This is a request for an LTQ-Orbitrap Mass Spectrometer 2D LC Proteomics System. The System will be used to characterize posttranslational modification in proteins regulating cell growth and division, transcription and other important events. Posttranslational modifications of proteins control their activity and interactions as well as their stability and degradation. The biological systems investigated range from cancer and retroviral regulation to neuronal survival and degeneration. The newly developed instrumentation requested possesses numerous advantages over previously available equipment for the characterization of protein modifications. The Fourier transform mass spectrometer affords high mass accuracy (<5 ppm) for both precursor and fragment ion measurements combined with high resolution (up to 60,000). These properties result in greatly enhanced confidence in protein identification. The equipment's ability to perform data dependent scans in both MS2 and MS3 mode is essential for the unambiguous characterization of phosphorylation sites. The sensitivity of both components of the mass analyzer, the linear ion trap and the Fourier transform Orbitrap, allows the detection of minor components and sub-stoichiometric modifications. The powerful data analysis system is indispensable for the analysis of complex data sets containing variable modifications. The equipment will greatly enhance the research of 7 major and 2 minor users at the Salk Institute whose work is supported by numerous NIH grants. [unreadable] [unreadable] [unreadable]